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ABSTRACTS – Symposia/Contributed Oral Papers
energy barriers throughout the reaction process, and have
a great effect on the function of the ligand after the reaction
process. Since the precise mechanism of interaction
between an enzyme and its ligand(s) is highly disputed, providing
additional insight into this phenomenon is of great
importance. Forced unbinding studies using atomic force
microscopy (AFM) have contributed valuable information
about the interactions between biomolecules. The strength
of intermolecular interactions can be observed by attaching
the enzyme and ligand molecules to the AFM tip and
sample surfaces through tethering molecules, and measuring
the unbinding force required to pull the molecules apart. By
applying a previously modified, freely jointed chain model,
along with additional mathematical analyses, we were able
to determine the unbinding mechanism in a model enzyme/
inhibitor system consisting of 5’-Methylthioadenosine/Sadenosylhomocysteine
nucleosidase and its transition state
analog, Homocysteinyl Immucillin A. Our data suggest that
in this system the unbinding mechanism follows a process
of elastic deformation. This type of observational method
has the potential to greatly improve our understanding of
enzymatic interactions as well as the production of powerful
inhibitory drugs.
103 Ab initio QM/MM Molecular Dynamics with AMBER and
TeraChem: Exploring Environmental Effects on the Absorption
Spectrum of Photoactive Yellow Protein, ANDREAS W
GOETZ (San Diego Supercomputer Center 10100 Hopkins
Drive, La Jolla, CA 92093; agoetz@sdsc.edu).
We have recently extended the mixed quantum mechanical
/ molecular mechanical (QM/MM) capabilities of the
AMBER molecular dynamics (MD) software package to
include ab initio and density functional theory (DFT) methods
via an interface to external QM software packages. Of
particular interest is our support of the electronic structure
code TeraChem that exploits the massive parallelism of GPU
accelerators to speed up ground and excited state calculations.
We describe the interface between AMBER and TeraChem
and present results for absorption spectra of photoactive
yellow protein (PYP) obtained from time-dependent
DFT calculations within the QM/MM framework along
MD trajectories. The effects of long-range electrostatics are
explored by computing the spectra for various QM regions
and MM cutoff values. Comparisons are made to spectra calculated
for the PYP chromophore in vacuum and aqueous
solution.
104 Characterizing the Conformations and Dynamics of
PEGylated Human Interferon ß-1a via Molecular Dynamics
Simulation, NIKOLAI SMOLIN (Department of Chemistry
and Biochemistry, Boise State University, 1910 University
Drive, Boise, ID 83725; nikolaismolin@boisestate.edu).
PEGylation, the covalent attachment of a polyethylene
glycol polymer to a molecule or protein, is known to increase
the efficacy of a protein with minimal changes to immunogenic
properties. The protein of interest in this study is human
interferon ß-1a (IFN), used in the treatment of multiple sclerosis,
cancer, and viral infection. The effect of PEGylation is
still poorly understood at the molecular level. In this work,
we present comparative molecular dynamics simulations of
free mPEG’s, Apo IFN, and mPEG-IFN conjugates in order
to describe and characterize the conformational differences
induced by PEGylation. The simulations allow deeper insight
into the dynamics and energetics of the mPEG-IFN interactions
not observable by conventional bench top experiments.
A major concern of pharmaceutic development is assessing
the stability of the system. We anticipate the findings of this
study will have broad implications for protein pharmaceutical
enhancement and development with a unique approach
to the study of protein drug stability from a computational
perspective.
contributed oral
PRESENTATIONS
Health Sciences Section
Monday, starting at 8:20 a.m. in WILLOWS 1
105 Psychoanalysis and Conflict Between the Mutual Nurturance
Drive and Social Survival, RODERIC GORNEY
(Department of Psychiatry, Semel Institute, UCLA, 760
Westwood Plaza, Los Angeles, CA 90095, [please send a
copy of correspondence to Dr. Gorney’s private office at 635
Walther Way, Los Angeles, CA 90049]; preadapt@ucla.edu).
Mutual nurturance begins at birth with breast suckling
that simultaneously nourishes the baby and, via reflex stimulation
of oxytocin in mother, halts her bleeding. We grow
up identifying with the care-giver and wanting to be mutual
nurturers too.
What I call the “mutual nurturance drive” developed
across three million years of human evolution in small
nomadic bands as our fundamental strategy for surviving
scarcity. Because they were each other’s only social security,
these early people mainly took care of each other by sharing.
Modern civilization began 12,000 years ago with invention
of agriculture/herding, which generated surpluses and
allowed settling in fixed villages. For the first time, people
could safely hoard for themselves rather than share with
neighbors whose resultant poverty converted them into the
most valuable resource of all: cheap labor.
Twelve millennia later, all our “advanced” societies,
whether “left” or “right,” continue to concentrate wealth and
power, so that now we instead increasingly take advantage
of each other, surviving not on good will, but on goods, as
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